Clinicopathologic features of invasive breast cancer (BC) diagnosed in carriers of germline PALB2, CHEK2 and ATM pathogenic variants.

Authors

null

Danika Scott

Stanford University School of Medicine, Stanford, CA

Danika Scott , Kerry Kingham , Rachel Hodan , Cindy Ma , Meredith Mills , James M. Ford , Allison W. Kurian , Melinda L. Telli

Organizations

Stanford University School of Medicine, Stanford, CA, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, Stanford Health Care, Stanford, CA, Stanford Cancer Institute, Stanford University School of Medicine, Palo Alto, CA, Stanford University, Stanford, CA, Stanford School of Medicine, Stanford, CA

Research Funding

Other Foundation
BRCA Foundation

Background: While germline pathogenic variants (PVs) in BRCA1/2 account for a large proportion of hereditary breast cancer (BC), PVs in PALB2, CHEK2 and ATM are increasingly detected. However, the phenotype and clinical features of invasive BC with these PVs have not been fully described. Methods: We identified patients with a PV or likely PV in PALB2, CHEK2 or ATM tested clinically at Stanford between 2014 - 2019 who provided informed consent to be included in a prospective cancer genetics registry. Data on baseline demographics, genetic testing history, and clinicopathologic features of diagnosed BC were collected. For patients with a subsequent diagnosis of metastatic BC, we calculated disease-free interval (DFI). Results: 130 patients met inclusion criteria for analysis: ATM (N=39), CHEK2 (N=58), PALB2 (N=33). Nearly all (98.5%) were women, with 2 male BC in ATM carriers. Non-Hispanic White ethnicity was most common in ATM (64.1%, 95% CI 48.4%-77.3%) and CHEK2 carriers (69.0%, 95% CI 56.1%-79.4%), but comprised only 39.4% (95% CI 24.7%-56.4%) in PALB2 carriers. Asian/Pacific Islander (24.2%, 95% CI 12.6%-41.3%) and Hispanic (30.3%, 95% CI 17.3%-47.5%) ethnicities were enriched among PALB2 mutation carriers. In total, 97.7% learned of their PV status only after a preceding diagnosis of BC and 43.1% were diagnosed with BC at age ≤ 45. Data regarding invasive BC subtypes, incidence of subsequent primary BC, and metastatic recurrence are listed below in the table. Additional data on stage, grade and sites of metastatic spread will be presented. Conclusions: We observed clinically important differences in the spectrum of BC subtypes among carriers of ATM, CHEK2 and PALB2 PVs, in addition to racial/ethnic differences with Asian/Pacific Islander and Hispanic ethnicity enriched among carriers of PALB2 PVs.

% ATM (N=39)95% CI% CHEK2 (N=58)95% CI% PALB2 (N=33)95% CI
Invasive BC Subtype71.8%56.1%-83.6%86.2%74.8%-93.1%60.6%43.7%-75.4%
    ER and/or PR positive, HER2-negative
    Any HER2-positive25.6%14.4%-41.2%13.8%6.9%-25.2%3%<0.01%-16.7%
    TNBC2.6%<0.01%-14.3%0.0%0.0%-7.4%36.4%22.1%-53.4%
Diagnosed with Subsequent Primary BC12.8%5.1%-27.2%19%10.8%-31.0%21.2%10.4%-38.1%
Diagnosed with Metastatic BC5.1%0.5%-17.8%17.2%9.4%-29.1%24.2%12.6%-41.3%
Percent Relapse-Free ≥ 5 years0%0.0%-48.9%50%23.7%-76.3%12.5%0.11%-49.2%
Median DFI (years)4.36.41.7

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Cancer Prevention, Risk Reduction, and Genetics

Track

Prevention, Risk Reduction, and Genetics

Sub Track

Cancer Genetics

Citation

J Clin Oncol 38: 2020 (suppl; abstr 1549)

DOI

10.1200/JCO.2020.38.15_suppl.1549

Abstract #

1549

Poster Bd #

41

Abstract Disclosures